Investigating the Role of C-type Lectin Receptor Dectin-2 in Schistosome Immunopathology
Open Access
Author:
Colon, Maria
Area of Honors:
Immunology and Infectious Disease
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
Parisa Kalantari, Thesis Supervisor Robert Paulson, Thesis Honors Advisor
Keywords:
Schistosomiasis Dectin-2 Inflammasome
Abstract:
Parasitic flatworm Schistosoma mansoni infects avian and mammalian hosts and results in schistosomiasis. Adult worms lay eggs in the bloodstream, and most eggs are excreted through host fecal matter. A fraction of the eggs fails to pass through and wedge in liver and intestinal tissue. The presence of dying eggs and egg antigens results in a CD4 T cell-mediated inflammatory response. In mild pathology, the cytokine environment is Th2-directed, while in severe pathology the Th1 and Th17 cytokine environments dominate. We and others have shown that IL-1β expression leads to severe pathology. Major C-type lectin receptors CD209a, Dectin-2, and Mincle are crucial for egg-mediated IL-1β production in dendritic cells (DCs) and macrophages. Although inflammasomes are known to be important in egg-mediated IL-1β production, it has remained unclear whether the C-type lectin receptors induce IL-1β production via inflammasome activation. Our findings establish Dectin-2 as a central inducer of inflammasome and immunopathology in murine schistosomiasis. Understanding pathways leading to inflammation can ultimately lead to the identification of novel targets for therapeutic intervention.
